The catalytic mechanisms of enzymes frequently requires the transfer of a proton from one residue to another. In addition, the buildup of proton gradients across membranes has been associated with proton hops along chains of H-bonded residues contained within transmembrane proteins. Quantum chemical methods will be used in this project to investigate the fundamental principles of the proton transfer reaction. As the three-dimensional structure of proteins makes for a wide diversity of different types and geometries of H-bonds, proton transfers will be studied for various pairs of residues and for each pair, a range of systematic variations in the H-bond geometry will be considered. The strategy of the project is such as to first carry out very sophisticated calculations including large basis sets and electron correlation on small model systems to extract in an accurate way the fundamental properties of the transfer process. In successive stages, the model systems will be progressively enlarged to more realistic models of true protein residues. The large body of systematic data obtained from these studies will be used to help understand means by which the protonation states of various residues can be controlled. Possible mechanisms by which conformational changes within the protein may be coupled to a "pushing" of a proton will be thoroughly explored. The effects of pH upon the process will be examined by comparison of proton transfer properties of various protonation states of appropriate residues (e.g. -COOH vs. -COO-). The effect of the protein environment upon the proton transfer will be monitored by including charged and polar groups in the vicinity of the H-bond as well as incorporating the response of the medium to the charge distribution within the H-bond.